Nebulized Colistin in Ventilator-Associated Pneumonia and Tracheobronchitis: Historical Background, Pharmacokinetics and Perspectives
Clinical evidence suggests that nebulized colistimethate sodium (CMS) has benefits for treating lower respiratory tract infections caused by multidrug-resistant Gram-negative bacteria (GNB). Colistin is positively charged, while CMS is negatively charged, and both have a high molecular mass and are...
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doaj-3ba2a4adc69c41bb9fb794a9467f0c8b2021-06-01T01:23:12ZengMDPI AGMicroorganisms2076-26072021-05-0191154115410.3390/microorganisms9061154Nebulized Colistin in Ventilator-Associated Pneumonia and Tracheobronchitis: Historical Background, Pharmacokinetics and PerspectivesYinggang Zhu0Antoine Monsel1Jason A. Roberts2Konstantinos Pontikis3Olivier Mimoz4Jordi Rello5Jieming Qu6Jean-Jacques Rouby7on behalf of the European Investigator Network for Nebulized Antibiotics in Ventilator-Associated Pneumonia (ENAVAP)Department of Pulmonary and Critical Care Medicine, Hua-Dong Hospital, Fudan University, Shanghai 200433, ChinaMultidisciplinary Intensive Care Unit, Department of Anaesthesiology and Critical Care, La Pitié-Salpêtrière Hospital, Assistance Publique Hôpitaux de Paris, Medicine Sorbonne University, 75012 Paris, FranceBiotherapy (CIC-BTi) and Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Hôpital Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, 75012 Paris, FranceIntensive Care Unit, First Department of Respiratory Medicine, School of Medicine, Sotiria General Hospital, National and Kapodistrian University of Athens, 15772 Athens, GreeceAnaesthesiology and Intensive Care Department, University Hospital of Poitiers, University of Poitiers, 86000 Poitiers, FranceCentro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, 28029 Madrid, SpainDepartment of Pulmonary and Critical Care Medicine, Rui-jin Hospital, Shanghai Jiao-tong University School of Medicine, Shanghai 200127, ChinaMultidisciplinary Intensive Care Unit, Department of Anaesthesiology and Critical Care, La Pitié-Salpêtrière Hospital, Assistance Publique Hôpitaux de Paris, Medicine Sorbonne University, 75012 Paris, FranceClinical evidence suggests that nebulized colistimethate sodium (CMS) has benefits for treating lower respiratory tract infections caused by multidrug-resistant Gram-negative bacteria (GNB). Colistin is positively charged, while CMS is negatively charged, and both have a high molecular mass and are hydrophilic. These physico-chemical characteristics impair crossing of the alveolo-capillary membrane but enable the disruption of the bacterial wall of GNB and the aggregation of the circulating lipopolysaccharide. Intravenous CMS is rapidly cleared by glomerular filtration and tubular excretion, and 20–25% is spontaneously hydrolyzed to colistin. Urine colistin is substantially reabsorbed by tubular cells and eliminated by biliary excretion. Colistin is a concentration-dependent antibiotic with post-antibiotic and inoculum effects. As CMS conversion to colistin is slower than its renal clearance, intravenous administration can lead to low plasma and lung colistin concentrations that risk treatment failure. Following nebulization of high doses, colistin (200,000 international units/24h) lung tissue concentrations are > five times minimum inhibitory concentration (MIC) of GNB in regions with multiple foci of bronchopneumonia and in the range of MIC breakpoints in regions with confluent pneumonia. Future research should include: (1) experimental studies using lung microdialysis to assess the PK/PD in the interstitial fluid of the lung following nebulization of high doses of colistin; (2) superiority multicenter randomized controlled trials comparing nebulized and intravenous CMS in patients with pandrug-resistant GNB ventilator-associated pneumonia and ventilator-associated tracheobronchitis; (3) non-inferiority multicenter randomized controlled trials comparing nebulized CMS to intravenous new cephalosporines/ß-lactamase inhibitors in patients with extensive drug-resistant GNB ventilator-associated pneumonia and ventilator-associated tracheobronchitis.https://www.mdpi.com/2076-2607/9/6/1154nebulized polymyxinnebulized colistimethate sodiumcolistinmultidrug resistant gram-negative bacteriaventilator-associated pneumoniaventilator-associated tracheobronchitis |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yinggang Zhu Antoine Monsel Jason A. Roberts Konstantinos Pontikis Olivier Mimoz Jordi Rello Jieming Qu Jean-Jacques Rouby on behalf of the European Investigator Network for Nebulized Antibiotics in Ventilator-Associated Pneumonia (ENAVAP) |
spellingShingle |
Yinggang Zhu Antoine Monsel Jason A. Roberts Konstantinos Pontikis Olivier Mimoz Jordi Rello Jieming Qu Jean-Jacques Rouby on behalf of the European Investigator Network for Nebulized Antibiotics in Ventilator-Associated Pneumonia (ENAVAP) Nebulized Colistin in Ventilator-Associated Pneumonia and Tracheobronchitis: Historical Background, Pharmacokinetics and Perspectives Microorganisms nebulized polymyxin nebulized colistimethate sodium colistin multidrug resistant gram-negative bacteria ventilator-associated pneumonia ventilator-associated tracheobronchitis |
author_facet |
Yinggang Zhu Antoine Monsel Jason A. Roberts Konstantinos Pontikis Olivier Mimoz Jordi Rello Jieming Qu Jean-Jacques Rouby on behalf of the European Investigator Network for Nebulized Antibiotics in Ventilator-Associated Pneumonia (ENAVAP) |
author_sort |
Yinggang Zhu |
title |
Nebulized Colistin in Ventilator-Associated Pneumonia and Tracheobronchitis: Historical Background, Pharmacokinetics and Perspectives |
title_short |
Nebulized Colistin in Ventilator-Associated Pneumonia and Tracheobronchitis: Historical Background, Pharmacokinetics and Perspectives |
title_full |
Nebulized Colistin in Ventilator-Associated Pneumonia and Tracheobronchitis: Historical Background, Pharmacokinetics and Perspectives |
title_fullStr |
Nebulized Colistin in Ventilator-Associated Pneumonia and Tracheobronchitis: Historical Background, Pharmacokinetics and Perspectives |
title_full_unstemmed |
Nebulized Colistin in Ventilator-Associated Pneumonia and Tracheobronchitis: Historical Background, Pharmacokinetics and Perspectives |
title_sort |
nebulized colistin in ventilator-associated pneumonia and tracheobronchitis: historical background, pharmacokinetics and perspectives |
publisher |
MDPI AG |
series |
Microorganisms |
issn |
2076-2607 |
publishDate |
2021-05-01 |
description |
Clinical evidence suggests that nebulized colistimethate sodium (CMS) has benefits for treating lower respiratory tract infections caused by multidrug-resistant Gram-negative bacteria (GNB). Colistin is positively charged, while CMS is negatively charged, and both have a high molecular mass and are hydrophilic. These physico-chemical characteristics impair crossing of the alveolo-capillary membrane but enable the disruption of the bacterial wall of GNB and the aggregation of the circulating lipopolysaccharide. Intravenous CMS is rapidly cleared by glomerular filtration and tubular excretion, and 20–25% is spontaneously hydrolyzed to colistin. Urine colistin is substantially reabsorbed by tubular cells and eliminated by biliary excretion. Colistin is a concentration-dependent antibiotic with post-antibiotic and inoculum effects. As CMS conversion to colistin is slower than its renal clearance, intravenous administration can lead to low plasma and lung colistin concentrations that risk treatment failure. Following nebulization of high doses, colistin (200,000 international units/24h) lung tissue concentrations are > five times minimum inhibitory concentration (MIC) of GNB in regions with multiple foci of bronchopneumonia and in the range of MIC breakpoints in regions with confluent pneumonia. Future research should include: (1) experimental studies using lung microdialysis to assess the PK/PD in the interstitial fluid of the lung following nebulization of high doses of colistin; (2) superiority multicenter randomized controlled trials comparing nebulized and intravenous CMS in patients with pandrug-resistant GNB ventilator-associated pneumonia and ventilator-associated tracheobronchitis; (3) non-inferiority multicenter randomized controlled trials comparing nebulized CMS to intravenous new cephalosporines/ß-lactamase inhibitors in patients with extensive drug-resistant GNB ventilator-associated pneumonia and ventilator-associated tracheobronchitis. |
topic |
nebulized polymyxin nebulized colistimethate sodium colistin multidrug resistant gram-negative bacteria ventilator-associated pneumonia ventilator-associated tracheobronchitis |
url |
https://www.mdpi.com/2076-2607/9/6/1154 |
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